The process of periodontal wound healing consists of a series of coordinated events involving cell migration, proliferation and differentiation of a variety of cells driven by locally released mediators. Normal tissue healing requires that the cells and mediators of the immune system, the connective tissue and the vascular endothelium coordinate to effect the repair process in a timely and efficient manner. An inflammatory response is an integral part of this process, at least in the adult. However in the fetus healing occurs rapidly without the inflammatory response leading to restoration of normal tissue architecture and function. Pro-inflammatory cytokines, IL-1 and TNF, have been proposed to play a major role in triggering this inflammatory response. The goal of present proposal is to test the hypothesis that the inflammatory response generated in periodontal wound healing by IL-1 and TNF affects negatively the subsequent phases of the healing events namely granulation tissue formation and matrix production and thereby the outcome of the healing process. To test this hypothesis we are proposing to block the activity of IL-1 and TNF using soluble receptors injected in a non-human primate periodontal wound healing model and determine how this intervention impacts on the subsequent phases of the wound process. To achieve this two aims are proposed: using immunohistochemistry, in situ hybridization and RT-PCR techniques, aim-1 will quantify the changes in inflammatory cell infiltrate, microvasculature density and in the amount of tissue repaired when IL-1 and TNF blockers are injected in periodontal wounds. In so doing we will attempt to draw a correlation between the IL-1 and TNF activity and the changes observed. Aim-2 will focus on gaining insight into the molecular mechanisms which underlie changes in granulation tissue and matrix formation when IL-1 and TNF soluble blockers are injected in periodontal wounds.